Jerry Silver and Other Discussion from ChinaSCINet Update

[jsilver]

[QUOTE=Wise Young;1634364]As I have said many times before, I don't think that we disagree on the phenomenon. We disagree on the terminology. I believe that the word "scar" should be reserved for situations when fibroblasts are present. In my opinion, the word "gliosis" should be used to refer to tissues where astrocytes have proliferated. I don't even oppose the term "glial scar", as long as it is applied to the situation when fibroblasts have invaded into central nervous tissue and formed a fibrous scar against which glial cells have proliferated.

Wise, I will never argue this issue again with you. This is it for me. I have made myself perfectly clear over and over and over. You are the odd man out on this issue and you can simply remain that way. Good luck with your trials but I can assure you that nobody will believe your claims of regeneration without decent data. I'm done with this semantic word game that you like to play. You have no idea what you are talking about and your arguments make no sense especially in a modern scientific world. Astrocytes are perfectly capable of building a wall without the presence of fibroblasts. No barrier is absolute. I thought I made that point quite clearly. You have the unmitigated gall to suggest that I don't understand the implications of the data from my own lab! Are you totally nuts? You use ancient or insufficient techniques and are far too liberal with the mechanistic conclusions you draw from your data. Bye Bye

[lynnifer]

Ouch.

Irregardless, I hope this works. It could save a lot of lives. Breathing restored ... bladder function alone would spare so many of constant infections (I hope?) and the ever present risk of sepsis and death. Not to mention the improved quality of life.

The only problem would be a female who can't transfer in time to pee!

"Since the 1800's ..." No one believed him. "1996 ... " No one believed him.

Just finished a 3 week course of Cipro which causes skin disruptions on old scars for me ... the leaking has stopped. I'll have some testing done on Monday. It appears to me though, now, that I am a ticking time bomb since using the foley in 2009. Colonized probably ... I'll have to be careful not to develop antibiotic resistance. This research is what I've waited so long for ...

[skeaman]

Dr jsilver

[QUOTE=jsilver;1634494]

As I have said many times before, I don't think that we disagree on the phenomenon. We disagree on the terminology. I believe that the word "scar" should be reserved for situations when fibroblasts are present. In my opinion, the word "gliosis" should be used to refer to tissues where astrocytes have proliferated. I don't even oppose the term "glial scar", as long as it is applied to the situation when fibroblasts have invaded into central nervous tissue and formed a fibrous scar against which glial cells have proliferated.

Wise, I will never argue this issue again with you. This is it for me. I have made myself perfectly clear over and over and over. You are the odd man out on this issue and you can simply remain that way. Good luck with your trials but I can assure you that nobody will believe your claims of regeneration without decent data. I'm done with this semantic word game that you like to play. You have no idea what you are talking about and your arguments make no sense especially in a modern scientific world. Astrocytes are perfectly capable of building a wall without the presence of fibroblasts. No barrier is absolute. I thought I made that point quite clearly. You have the unmitigated gall to suggest that I don't understand the implications of the data from my own lab! Are you totally nuts? You use ancient or insufficient techniques and are far too liberal with the mechanistic conclusions you draw from your data. Bye Bye

Befour
you go any where thank you for your in put on this i am not taking any sides . For it is all to complicated for me to understand all i would like to know is will it work
Can i ask you when do you hope to bring you work to Human trials sorry if this was ask befour

[ay2012]

The trials are underway, they're going for Phase III, and I don't know what to think given Dr. Silvers criticisms. But, if function is being restored and its safe, the mechanism isn't quite that important. Which is why I hope some detailed information of the recent 6 month data is provided to the community, either here or in a journal. It would go a long way to alleviating the fears that understandably arise when you have another respected scientist in the field saying "this will not work". Of course, if the therapy proves ineffective we'll all be going back to those words and will have wished we took the criticisms a little more seriously. I totally support the idea of a clinical trial network to test the most promising therapies... But dollars are scarce. Again, hoping the treatment proves effective...

[Steven Edwards]

Dr. Silver,

May I ask what, in your opinion, is the significance of the different terminology you and Wise use to describe the glial barrier?

After reading this:

Source:

Scar formation A glial scar forms after injury to the CNS and acts as a barrier to regenerating neurons (Figure 1). Glial scars consist mainly of reactive astrocytes, which become hypertrophic and greatly increase their expression of intermediate filament proteins such as vimentin and glial fibrillary acidic protein. Reactive astrocytes and oligodendrocyte precursor cells (OPCs) have been shown to upregulate their expression of scar-associated inhibitory CSPGs such as neurocan, phosphacan and versican [8]. Interestingly, the expression of both growth-inhibitory and growth-promoting ECM molecules increases in reactive astroglia, but the inhibitory ECM components are more markedly upregulated [11]. In more severe injuries resulting in breakdown of the meninges, connective tissue elements, such as fibroblasts, mix with astrocytes and other invading cells, including macrophages, in the lesion [12]. Development of the scar begins within hours of injury, and a correlation among the areas of most significant BBB breakdown, highest infiltration of activated macrophages and greatest glial scar formation has been demonstrated [13]. Reactive microglia and OPCs are recruited to the forming scar, where they proliferate [8]. Immediately after injury, astrocytes undergo a process known as ‘reactive gliosis’. Transgenically targeted ablation of the dividing population of reactive astrocytes after spinal cord injury (SCI) prevents reestablishment of the BBB, resulting in an increase in lesion size, cell death, an exacerbated immune response and marked motor deficits [14]. Thus, despite its inhibitory properties, the glial scar is vital to seclusion of the damaged site and to protection of the surrounding regions from secondary injury. (Source)

A better question might be: what differentiates 'reactive gliosis' from a 'glial scar'? (Is 'reactive gliosis' the process by which a 'glial scar' forms?)

Best,

Steven

[Christopher Paddon]

I think Jerry has answered this - in simple terms Jerry says the 'scar' has to be dealt with in some way before any bridging therapy can succeed whereas Wise thinks just transplanting cord blood cells or some other cells into the injury site may be enough. The question we can ask ourselves is how many scientists agree with Wise and how many agree with Jerry.

[Tyran21]

In the recent Wise's trial, Dr Wise said nerve bundle grew across the injury site.Is this a case of nerve growing across the scar? Is Dr J.Silver trying to say if Dr Wise remove the scar,the result will be better? Confuse, can someone correct me if i'm wrong. Thanks in advance.

[topperf]

.. Pride.. Such a potent emotion. And sad to see two intellectual capacities not being able to agree to disagree. I can't help but think of the words sung by Presley a long time ago: "a little less conversation and a little more action, please. All this aggravation ain't satisfactioning me"

http://www.youtube.com/watch?v=Zx1_6F-nCaw

[quadfather]

The saddest part of this exchange/discussion is that highlights just how very far we are from treatments that will help us.

A very long way...

[crabbyshark]

The question we can ask ourselves is how many scientists agree with Wise and how many agree with Jerry.

A lot of experts made the same argument when rumors first leaked about the Earth being round.

Every single scientist in the world could claim "stem cell injection without an implanted scaffold fails to regenerate spinal cord" but it doesn't mean much if one of them tries it out and somehow it works.

[crabbyshark]

I'm done with this semantic word game that you like to play.

Semantics are important. Most of us here have spinal cord injury. There is a big difference between a C-5/6 ASIA B and a T-9 ASIA A. Like any other medical description, why shouldn't different types of scars be classified under different names?

Yes, indeed, the scar does change over time. It becomes thinner and its associated inhibitory proteoglycan extracellular matrices become more restricted to the cell surfaces. In some very severe contusive injuries, Schwann cells eventually invade through the dorsal portion of the scar and enter the core of the lesion. It is unknown how they do this. Schwann cells are extremely growth promoting and they provide a scaffold for axonal growth, mostly of sensory axons from the roots, that can pass through the scar wall and into the core of the lesion. This phenomenon demonstrates that the scar is not totally but only relatively impenetrable. However, the presence of axons in the lesion core does not mean that scar does not exist but, rather, that over time the scar changes and one of these changes is that Schwann cell invasion occurs. However, axons do not pass completely through the lesion as Wise suggests but only into the lesion core where they remain trapped and functionally useless.

Schwann cells/axons penetrate the scar and get into the core of the lesion. It is unknown how they do this.

Could a potent cocktail of stem cells, methylprednisolone, and lithium perhaps do the same thing, maybe even exponentially better?

[crabbyshark]

The saddest part of this exchange/discussion is that highlights just how very far we are from treatments that will help us.

A very long way...

There is a clinical trial being done in which people are being injected with stem cells. This has never. been. done. before. Even if people failed to show improvement, its proven safety alone is a big deal. Dr. Wise says he thinks he's observed some improvements. The study will be published sometime in the coming months. What about scientists arguing makes you think we are "a very long way..." from treatments that will help us?

Dr. Silver has dedicated 30 years working to overcome the scar. If the UCBMC therapy with no implanted scaffold works, that might indicate overcoming the scar (at least in some cases) isn't that big of a deal. If I were Dr. Silver I'd probably be a little salty too. He's contributed a lot to SCI research.

[Tyran21]

Even better if he could come out with a trial to show removing the scar shows better results.It will only benefits towards finding a cure more.

[Christopher Paddon]

A lot of experts made the same argument when rumors first leaked about the Earth being round.

Every single scientist in the world could claim "stem cell injection without an implanted scaffold fails to regenerate spinal cord" but it doesn't mean much if one of them tries it out and somehow it works.

If we rely on actual published peer reviewed animal research studies in good scientific journals and clinically relevant data to help with SCI recovery we should find whether or not the scar is a barrier and perhaps eventually therapies that will overcome all the obstacles to regeneration.

[quadfather]

There is a clinical trial being done in which people are being injected with stem cells. This has never. been. done. before. Even if it fails, it's a big deal. Dr. Wise says he thinks he's observed some improvements. The study will be published sometime in the coming months. What about scientists arguing makes you think we are "a very long way..." from treatments that will help us?

Dr. Silver has dedicated 30 years working to overcome the scar. If the UCBMC therapy with no implanted scaffold works, that might indicate overcoming the scar (at least in some cases) isn't that big of a deal. If I were Dr. Silver I'd probably be a little salty too. He's contributed a lot to SCI.

Clinical trials for chronics is a big deal. Just like the University of Florida embryonic tissue trial on chronics done in the 90s and the Diacrin stem cell trial on chronics done 12 years ago (BTW both failed). My point is that we need more trials for chronics. Let's do that rather than this. We 1000 trials per day to be starting. Then maybe one will hit.